OPEN ACCESS
Principles for protecting integrity
in the conduct and reporting
of clinical trials
January 24, 2007
Issue
Public concern is high regarding the timely and complete reporting of clinical trial results, primarily when
the trials are sponsored by the drug, biologicals, or device industries. Because academic researchers
and their institutions often play a prominent role in such trials, these concerns challenge the integrity of
the academic medical research community as well as the sponsors of the trials.
Background
A number of external initiatives have heightened standards for reporting clinical trial results, yet there is
evidence that significant variation continues to exist within the research community over the application
of appropriate standards for analyzing and reporting the results of sponsored clinical research,
especially clinical trials sponsored by industry. We propose a set of principles, recommendations, and
guidelines, rooted in sound science and sound ethics, to guide medical schools, teaching hospitals,
departments of public health, professional societies, industry, drug licensing authorities, government
research and policy-making bodies, non profit sponsors of clinical trials, patient advocacy groups, and
ultimately, the entire health care community.
Consensus Principles
The following principles should apply to the conduct of all clinical trials regardless of the source of
funding. They encompass single site as well as multisite studies, although operationalization of the
principles may differ across study types and sizes. For purposes of these principles, “clinical trials”
should be defined by reference to the International Committee of Medical Journal Editors (ICMJE)
definition: “Any research project that prospectively assigns human subjects to intervention and
comparison groups to study the cause-and-effect relationship between a medical intervention and a
health outcome.” “Medical intervention” means “any intervention used to modify a health outcome”,
including “drugs, surgical procedures, devices, behavioral treatments, process-of-care changes, and
the like.”1 This definition explicitly excludes phase 1 and early phase 2 studies (but not all late phase 2
studies), and it includes all phase 3 and 4 clinical trials, including studies of new indications for
approved products.
Publications and Public Availability of Research Results
1. Researchers and their institutions have an ethical obligation when conducting human research
to seek to make the results available publicly.
1
DeAngelis, C. et al., Is This Clinical Trial Fully Registered. JAMA. 2005; 293: 2927-9. DeAngelis, C. et al., Clinical Trial
Registration: a Statement from the International Committee of Medical Journal Editors. N.Engl.J.Med. 2004; 351:1250-1.
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Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials
2. Contracts between sponsors and institutions for conducting clinical trials should require a good
faith effort to publish the results of such trials in a peer reviewed journals in a timely fashion.
3. Contracts for clinical trials should contain a commitment of adequate funding to cover the full
costs of the analysis defined in the protocol and the costs associated with publishing the results.
This principle applies even when the study is terminated for any reason prior to meeting its prespecified objectives.
4. All trials meeting the ICMJE requirements2 for registration should make their results publicly
available, by means of a link to any peer reviewed publications and by posting the results in an
online accessible repository, within 18 months of submission of a manuscript for publication.
5. After publication of the results, the sponsor, the investigators, and their institutions should adopt
a model for public sharing of the data underlying publications (for example, one used by the
NIH3) which permits exceptions for confidential or proprietary information.
Registration of Clinical Trials
6. Within 21 days of initiating enrollment of participants, any clinical trial covered by these
principles should be fully registered pursuant to the ICMJE requirements4 for registration.
Registration must include the assignment of a unique identifying number to each clinical trial.
7. Registration should be accomplished in a national or regional registry meeting minimum quality
standards and should include all the elements required by that registry.
8. Insofar as it is feasible and allowed by the register, trial registration data should be regularly
updated to include a link to all published reports associated with the study.
Lead Investigator and Steering Committee
9. A multisite clinical trial, at the outset, should identify a lead or principal investigator and a
steering committee to represent the full body of investigators.
Publication and Analysis Committee
10. A multisite clinical trial, at the outset, should establish a publication and analysis committee
[hereinafter P&A committee]. It is essential that the P&A committee be independent of the
sponsor’s control, have access to the full data set, understand and implement the prespecified
analysis plan, and have the resources and skills both to interpret that analysis and perform
additional analysis if required. In order to prevent any appearance of undue influence by the
sponsor, the P&A committee should contain a majority of participating, non-sponsor-employed
investigators, with appropriate skills in analysis and interpretation of clinical trials. The P&A
committee and the steering committee may have the same membership.
2
Ibid. The World Health Organization is leading an international effort to provide a global portal for clinical trials registration.
Because the WHO effort has not yet been launched, the WHO effort is currently acknowledged but not included as an
alternative to the ICMJE registration requirements.
3 http://grants.nih.gov/grants/policy/data_sharing/.
4 See note 1.
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Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials
11. The P&A committee in multisite clinical trials (or the principal investigator of single site studies),
through a qualified expert of its choosing, preferably a member of that committee, should have
the right to access any data generated during the study that the committee deems necessary to
ensure the integrity and validity of the study and its full reporting.
12. The P&A committee in multisite clinical trials (or the principal investigator in single site studies)
should require that the sponsor of the study perform its analysis of trial data in a defined period
of time. The committee (or PI) should be able to conduct its own analysis through an expert
selected by it, to the extent it deems this necessary. Whenever feasible, the expert should be
agreed upon by the P&A committee and the sponsor.
13. The sponsor should share with the P&A committee all analyses called for by the study that the
sponsor conducts of any biological materials it receives during the course of the study.
14. The P&A committee or PI should make a good faith effort to disseminate the results of the study
through peer reviewed mechanisms.
Individual Publication
15. Site-specific publications in multisite trials have an unavoidable potential for bias. Because they
are almost never part of the original analytic plan, they are often misleading, and should be
strongly discouraged. However, to respect an academic institution’s commitment to academic
freedom, site-specific analyses should nonetheless be permitted with conditions. Accordingly,
an individual site investigator in a multisite trial should be free to analyze and publish data from
the individual site, consistent with sound principles of science and analysis, but only after review
and comment by the P&A committee and only after publication of the study as a whole, or, in
the absence of acceptance of the full publication, within 2 years from the specified end points or
earlier termination of the study.
Authorship
16. Ghost or guest authorship is unacceptable. Authorship implies independent, substantial, and
fully disclosed participation in the study and in the preparation of the manuscript. It is
acceptable for employees of the sponsor to participate in drafting and publication activity, but
only if their roles are fully disclosed.
17. Institutions conducting clinical trials should adopt as policy the standards of authorship defined
by the ICMJE.
18. Where applicable, investigators should use the CONSORT principles5 as guidance for
publication of trial results.
19. Investigators should fully disclose, and journals should publish, the existence of all relevant
financial interests, including consultancies of any investigator, in all communications of trial
results.
5
Altman, D. et al., The Revised CONSORT Statement for Reporting Randomized Clinical Trials: Explanation and Elaboration.
Annals of Internal Medicine. 2001; 134: 663-94. Ioannidis, J. et al., Better Reporting of Harms in Randomized Trials: An
Extension of the CONSORT Statement. Annals of Internal Medicine. 2004; 141: 781-8.
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Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials
20. Any manuscript submitted for publication should accurately disclose the role of each author in
conducting the study and preparing the manuscript. Such information should also be disclosed
in any public presentation of study results, to the extent practicable.
21. Manuscripts submitted for publication should disclose all previous publications involving the
same protocol or database.
22. Manuscripts submitted for publication should be accompanied by the protocol and pre-specified
analysis plan and all dated amendments to them, and any deviations to the pre-specified plan
should be identified and discussed.
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Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials
Signatories
Individuals
Robert Alpern, M.D.
Dean
Yale University School of Medicine
Michael B. Amey
Associate Dean, Research Administration
Johns Hopkins University School of Medicine
Robert Califf, M.D.
Clinical Research Institute
Duke University Medical College
Arthur L. Caplan, Ph.D.
Chair of the Department of Medical Ethics
Director, Center for Bioethics
University of Pennsylvania
Gail H. Cassell, Ph.D.
Vice President of Infectious Diseases
Eli Lilly and Company
Kay Dickersin, Ph.D.
Professor
Johns Hopkins Bloomberg School of Public
Health
Robert N. Golden, M.D.
Vice Dean
Professor and Chair of Psychiatry
The School of Medicine
University of North Carolina Chapel Hill
Harry B. Greenberg, M.D.
Senior Associate Dean for Research
Acting Co-Chairman, Department of Medicine
and Microbiology and Immunology
Stanford University School of Medicine and the
VAPHCS
Stephen I. Katz, M.D., Ph.D.
Director
National Institute of Arthritis and
Musculoskeletal and Skin Diseases
Drummond Rennie, M.D.
Deputy Editor, JAMA
Adjunct Professor
University of California, San Francisco
Robert R. Rich, M.D.
Vice President and Dean
School of Medicine
University of Alabama at Birmingham
Brian L. Strom, M.D., M.P.H.
Chair and Professor
Dept. of Biostatistics and Epidemiology
Director
Center for Clinical Epidemiology and
Biostatistics
University of PA School of Medicine
Robert Temple, M.D.
Associate Director for Medical Policy
Food and Drug Administration
DHHS/FDA/CDER/OMP
Janet Wittes, Ph.D.
President
Statistics Collaborative
Alastair J.J. Wood, M.D.
Associate Dean
Professor of Medicine
Clinical Pharmacology Division
Professor of Pharmacology
Vanderbilt University
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Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials
Writing Committee Chairs
David Korn, M.D.
Senior Vice President
Division of Biomedical and
Health Sciences Research
Association of American Medical Colleges
Susan Ehringhaus, J.D.
Assistant Vice President, Associate General
Counsel for Regulatory Affairs
Division of Biomedical and
Health Sciences Research
Association of American Medical Colleges
Endorsing Organizations
Association of American Medical Colleges
American College of Epidemiology
American College of
Neuropsychopharmacology
American Heart Association
American Medical Association
American Pediatric Society
American Society for Bone and Mineral
Research
Association of Medical School Pediatric
Department Chairs
Calcified Tissue International
Federation of American Societies for
Experimental Biology
Journal of Bone and Mineral Research
Society for General Internal Medicine
Society for Pediatric Research
The BlueCrossBlueShield Association and all
38 BCBS Plans in the United States
University of Alabama School of Medicine
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